Umberto Gelatti

Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome.

Objective: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-seropositive individuals. The aim of the study was to compare the main features of HCC in HIV-seropositive individuals with those in to HIV-negative patients. Patients and methods: All HIV-infected subjects with a diagnosis of HCC included in three cancer registry databases were enrolled in the study as cases. HCC cases that occurred in the province of Brescia, North Italy, in the period 1995–1998 and all cases reported at the Italian Liver Cancer Project were enrolled as controls. All data were collected using a standardized case report form. The main clinical and epidemiological characteristics of patients with HCC and their survival were compared between HIV-positive and uninfected subjects. Results: Forty-one HIV-infected subjects with HCC were identified. Multivariate analysis adjusted for age and sex identified an association between HIV infection and HCV infection [odds ratio (OR), 11; P = 0.005], and infiltrating tumours and/or extranodal metastasis at presentation (OR = 11.8; P < 0.001). HIV infection was independently associated with shorter survival (hazard ratio, 1.63; P = 0.015). Conclusions: HCC in HIV-infected patients is mainly associated with underlying chronic hepatitis C and has a more aggressive clinical course. Thus, preventative strategies (including the treatment of hepatitis C) should be implemented in the management of HIV/HCV-coinfected patients.

Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy.

Objective: Intrahepatic cholangiocarcinoma (ICC) is a rare type of primary liver cancer (PLC) arising from intrahepatic bile ducts. We carried out a case–control study to assess the association between ICC and hepatitis B and C virus (HBV and HCV) infections, alcohol intake, and hepatolithiasis in Brescia, North Italy. Methods: Among 370 subjects with histology-based diagnosis of PLC who were resident in the area and hospitalized in 1995–2000, 26 (7%) ICC cases were identified. A total of 824 subjects unaffected by hepatic diseases and frequency-matched with PLC cases by age, sex, date, and hospital of admission were recruited as controls. Results: Among ICC cases the mean age was 65 years, 80.8% were males, and 38.5% had cirrhosis. Seropositivity for anti-HCV, HBsAg, alcohol intake > 80 g/day and history of hepatolithiasis were found in 25%, 13%, 23.1%, and 26.9% of ICC cases and in 5.8%, 6.7%, 32.9%, and 10.6% of controls, respectively. The odds ratios adjusted for demographic factors by logistic regression (95% confidence interval; 95% CI) were 9.7 (1.6–58.9) for anti-HCV, 2.7 (0.4–18.4) for HBsAg, and 6.7 (1.3–33.4) for hepatolithiasis, whereas no association was found with alcohol drinking. Conclusions: HCV and hepatolithiasis may be risk factors for ICC in Western countries.

GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high‐risk population

Tobacco smoking and occupation are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. Glutathione S‐transferase (GST) M1, T1 and P1 are involved in the detoxification of PAH reactive metabolites. Two N‐acetyltransferase isozymes, NAT2 and NAT1, have major roles in catalyzing the N‐acetylation and O‐acetylation of aromatic amines. Cytochrome P450 1B1 (CYP1B1) and sulfotransferase 1A1 (SULT1A1) are also involved in the metabolism of PAHs and aromatic amines. It is hypothesized that the genetic polymorphisms of these metabolic enzymes have an effect on the individual susceptibility to bladder cancer in particular by interacting with relevant environmental exposures. A hospital‐based case‐control study among men in Brescia, Northern Italy recruited 201 incidence cases and 214 controls from 1997–2000. Occupational exposures were blindly coded by occupational physicians. Genotyping of polymorphisms were carried out with PCR‐RFLP method. Unconditional multivariate logistic regression was applied to model the association between genetic polymorphisms and bladder cancer risk. Effect modifications by age of onset, smoking and occupational exposures to PAHs and aromatic amines were evaluated. We also conducted an analysis of interaction between genetic factors. GSTM1 and GSTT1 null genotype were associated with an increased risk of bladder cancer with an odds ratio (OR) of 1.69 (95% confidence interval [CI] = 1.11–2.56) and 1.74 (95% CI = 1.02–2.95), respectively. The effect of GSTM1 null was seen particularly in heavy smokers, and there was a combined effect with occupational exposure of aromatic amines (OR = 2.77, 95% CI = 1.08–7.10). We observed a trend (p‐value < 0.01) of increasing cancer risk comparing subjects with normal GSTM1 and T1 activity to subjects with one (OR = 1.82, 95% CI = 1.16–2.85) or both null genotypes (OR = 2.58, 95% CI = 1.27–5.23). NAT2 slow acetylator was associated with marginally increased risk of bladder cancer (OR = 1.50, 95% CI = 0.99–2.27), and the OR for the joint effect with occupational exposure of aromatic amines was 3.26 (95% CI = 1.06–9.95). SULT1A1 Arg213His polymorphism showed a marginal protective effect. These findings suggest that individual susceptibility to bladder cancer may be modulated by GSTM1, GSTT1 and NAT2 polymorphisms.

Case‐control study on hepatitis C virus (HCV) as a risk factor for hepatocellular carcinoma: The role of HCV genotypes and the synergism with hepatitis B virus and alcohol

We performed a case‐control study to evaluate the risk of hepatocellular carcinoma (HCC) for hepatitis C virus (HCV) infection. A total of 305 newly diagnosed HCC cases (80% males) and 610 subjects (81% males) unaffected by clinically evident hepatic disease admitted to the 2 main hospitals in Brescia, North Italy, were recruited as cases and controls, respectively. Among the 122 HCC cases positive for HCV RNA, genotype 1b was found in 83 patients (68%), genotype 2 in 36 (29.5%) and genotype 1a in 3 (2.5%). Among the controls, 15 were infected with genotype 1b and 15 with type 2. Analysis of HCV envelope 1 nucleotide sequence among 25 cases and 8 controls infected with genotype 2 showed subtype 2c in 96% of cases and in all controls, and subtype 2a in 1 HCC case. The odds ratio (OR) for HCV RNA positivity adjusted for hepatitis B virus (HBV) markers and alcohol intake was 26.3 [95% confidence interval (CI): 15.8–44], and it was higher for genotype 1b (OR = 34.2) than type 2 (OR = 14.4). The OR for HCV RNA was 35.6 (95% CI: 14.5–87.1) when the HBV markers were all negative and 132 (15.3–890) when HBsAg positivity was present; the OR was 26.1 (95% CI: 12.6–54.0) among subjects with alcohol intake of 0–40 g/day and increased to 62.6 (23.3–168) and 126 (42.8–373) with an alcohol intake of 41–80 and >80 g/day, respectively. In conclusion, synergism was found between HCV infection and HBV infection and alcohol intake in causing HCC. Int. J. Cancer 81:695–699, 1999.

Bladder cancer, tobacco smoking, coffee and alcohol drinking in Brescia, northern Italy

The association between tobacco smoking, the consumption of coffee and alcohol and bladder cancer was investigated in a hospital-based case-control study in Brescia, northern Italy. A total of 172 incident cases (135 men and 37 women) and 578 controls (398 men and 180 women) were enrolled. As expected, cigarette smoking was strongly associated with bladder cancer. The odds ratios (OR) for coffee drinking adjusted for age, education, residence and cigarette smoking in current drinkers were 2.6 (95% confidence interval, CI: 1.1–6.1) in men and 5.2 (95% CI: 1.0–30.4) in women. A dose-response relationship was found in men, with the highest risk in the highest category of exposure: drinkers of more than 5 cups per day had an OR of 4.5 (95% CI: 1.2–16.8). The ORs for current alcohol drinkers were 2.1 (95% CI: 1.0–4.8) in men and 3.4 (95% CI: 1.2–9.7) in women; according to grams of ethanol drunk per day (grams/day, g/d) the ORs were: 1.7 (1–20 g/d), 1.6 (21–40 g/d), 4.3 (41–60 g/d) and 4.6 (61+ g/d) in men and 3.1 (1–20 g/d) and 3.9 (21+ g/d) in women. These results suggest that regular consumption of both coffee and alcohol can be independently associated with an increased bladder cancer risk.

Monitoring airborne genotoxicants in the rubber industry using genotoxicity tests and chemical analyses.

This research was designed to examine the presence of mutagenic/carcinogenic compounds in airborne pollutants in the rubber industry using an integrated chemical/biological approach. Inhalable airborne particulate matter (PM-10: <10 microm) was collected in four rubber factories using a high-volume sampler equipped with a cascade impactor for particle fractionation. The organic extracts of two different fractions (0.5-10 microm and <0.5 microm) were examined for mutagenicity with the Ames test and for in vitro DNA-damaging activity in human leukocytes by single-cell microgel electrophoresis (Comet assay). The extracts were also studied by gas chromatography/mass spectrometry (GC/MS) for polycyclic aromatic hydrocarbon (PAH) content. Nitrosamines in ambient air were sampled on cartridges and analysed by GC with a thermal energy analyser (TEA) detector. Airborne volatile genotoxins were monitored in situ using a clastogenicity plant test (Tradescantia/micronuclei test). The results showed that airborne particulates were mainly very fine (<0.5 microm) and that trace amounts of genotoxic nitrosamines (N-nitrosodimethylamine: 0.10-0.98 microg/m(3); N-nitrosomorpholine: 0.77-2.40 microg/m(3)) and PAH (total PAH: 0.34-11.35 microg/m(3)) were present in air samples. Some extracts, particularly those obtained from the finest fractions, were mutagenic with the Ames test and genotoxic with the Comet assay. In situ monitoring of volatile mutagens using the Tradescantia/micronuclei test gave positive results in two working environments. The results showed the applicability of this integrated chemical-biological approach for detecting volatile and non-volatile genotoxins and for monitoring genotoxic hazards in the rubber industry.

Bladder cancer, GSTs, NAT1, NAT2, SULT1A1, XRCC1, XRCC3, XPD genetic polymorphisms and coffee consumption: a case–control study

The aim of the study was to investigate NAT1, NAT2, GSTM1, GSTT1, GSTP1, SULT1A1, XRCC1, XRCC3 and XPD genetic polymorphisms, coffee consumption and risk of bladder cancer (BC) through a hospital-based case–control study. The study population included 197 incident BC cases and 211 controls. The association between genetic polymorphisms, coffee drinking and BC risk was assessed by logistic regression taking into account age, education, tobacco smoking and occupational exposures to polycyclic aromatic hydrocarbons and aromatic amines. No association was found between the genetic polymorphisms investigated and BC risk according to coffee consumption apart of a significant increased BC risk among GSTP1 105-114 Val carriers heavy coffee drinkers (>3 cups/day) (OR 3.18, 95%CI 1.06–9.55). In conclusion our findings suggest a very limited role, if any, of genetic polymorphisms investigated in modulating the BC risk in coffee drinkers.

Primary liver cancer and occupation in men: A case‐control study in a high‐incidence area in northern Italy

The objective of our study was to evaluate the association between occupation and risk of liver cancer. A hospital‐based case‐control study was carried out during 1997–1999 in the Province of Brescia, a highly industrialized area in Northern Italy with a high incidence of this neoplasm. The cases were 144 male patients with incident liver cancer (96% hepatocellular carcinoma). Controls were 283 male patients, matched to cases on age (±5 years), period and hospital of admission. Information on lifetime occupational history and alcohol consumption was obtained via interview. Specific occupational exposures to pesticides, solvents and other suspected hepatocarcinogens were evaluated. A blood sample was collected to detect hepatitis B and C infections. Odds ratios (OR) of occupational exposure and 95% confidence intervals (CI), adjusted for age, residence, education, heavy alcohol intake, hepatitis B surface antigen and hepatitis C virus antibodies positivity were computed. A statistically significant increased OR was observed for employment in repair of motor vehicles (OR 3.7; 95% CI 1.1–12.3; 9 exposed cases, 10 exposed controls). Increased ORs, although not statistically significant, were found for field‐crop farm workers, food and beverage processors, blacksmiths and machine‐tool operators, electrical fitters, clerical workers, manufacture of industrial machinery and personal and household services. A slightly increased OR was noted in workers exposed to toluene and xylene (OR 1.4; 95% CI 0.7–3.0, 23 cases, 36 controls); the OR was 2.8 (95% CI 1.0–7.6, 11 cases, 12 controls) for 20 or more years of exposure and 2.0 (95% CI 0.9–4.1, 21 cases, 28 controls) for 30 or more years of time since first exposure. The increase in OR seemed to be independent from that of alcohol or viral infections. Our study showed that the role of occupational exposures in liver carcinogenesis is limited. However, prolonged exposure to organic solvents such as toluene and xylene may represent a risk factor for liver cancer.

A case-control study on family history of liver cancer as a risk factor for hepatocellular carcinoma in North Italy

Objectives: We carried out a case–control study to investigate the role of history of liver cancer in a first-degree relative as a risk factor for hepatocellular carcinoma (HCC).Methods: Two hundred eighty-seven HCC incident cases and 450 subjects unaffected by liver disease (controls) were enrolled in the study. Family history of liver cancer and other malignancies and history of alcohol intake were collected by face-to-face interview. Blood samples were analyzed for HBsAg, anti-HCV and HCV RNA positivity.Results: Family history of liver cancer was associated with HCC (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.2–4.7), whereas family history of other malignancies was not (OR = 1.0; 95% CI = 0.6–1.5). An increased OR for family history of liver cancer was found among subjects negative for the other risk factors (OR = 2.0; 95% CI = 0.6–6.9). A synergism of family history of liver cancer was also evident with hepatitis B and hepatitis C virus infection and with heavy alcohol intake.Conclusions: This study suggests a role of family history independent from and interacting with known risk factors for hepatocellular carcinoma.

Cyberdrugs: a cross-sectional study of online pharmacies characteristics

As e-commerce and online pharmacies (OPs) arose, the potential impact of the Internet on the world of health shifted from merely the spread of information to a real opportunity to acquire health services directly. Aim of the study was to investigate the offer of prescription drugs in OPs, analysing their characteristics, using the content analysis method. The research performed using the Google search engine led to an analysis of 118 online pharmacies. Only 51 (43.2%) of them stated their precise location. Ninety-six (81.4%) online pharmacies did not require a medical prescription from the customers physician. Online pharmacies rise complex issues in terms of patient-doctor relationship, consumer empowerment, drug quality, regulation and public health implications.